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J Sato

Publications and source records attributed to J Sato.

At least 163 records · Page 9Linked to original sources

Simple, rapid and sensitive method for the determination of indomethacin in plasma by high-performance liquid chromatography with ultraviolet detection.

A micro method for determination of indomethacin in plasma was developed. Following deproteinization of plasma with acetonitrile containing internal standard (mefenamic acid), the separation of indomethacin and internal standard was achieved by high-performance liquid chromatography using a 7 microm LiChrosorb-RP18 column (250x4 mm I.D.) at 50 degrees C. The mobile phase was 6 mM phosphoric acid-acetonitrile (50:50). The flow-rate was kept at 2.0 ml/min and the column effluent was monitored at 205 nm. The coefficients of variation of the method estimated at 0.2 and 1.0 microg/ml were 4.2 and 2.3%, and the detection limit of the drug was about 0.05 microg/ml (S/N=5). The method requires minimum pretreatment of the plasma with a small sample volume (25 microl), and is very suitable for therapeutic drug monitoring of indomethacin in premature infants with symptomatic patent ductus arteriosus.

Chromatography, High Pressure Liquid↗

A possible role of endogenous inhibitor for nitric oxide synthesis in the bovine ciliary muscle.

The present experiments were designed to investigate the possible role of endogenous methylarginine derivatives such as NG-monomethyl-L-arginine, asymmetrical NG,NG-dimethyl-L-arginine and symmetrical NG,N'G-dimethyl-L-arginine for the nitric oxide synthesis in the bovine ciliary muscle. The contents of asymmetrical NG,NG-dimethyl-L-arginine and symmetrical NG,N'G-dimethyl-L-arginine in the bovine ciliary muscle were determined to be 370.2 +/- 27.6 (n = 5) and 182.4 +/- 22.9 (n = 5) pmoles g-1 wet weight, respectively by means of the automated high-performance liquid chromatography. NG-Monomethyl-L-arginine was below the assay limits. On the basis of the total tissue water content (0.792 +/- 0.006 ml g-1 wet weight, n = 14), the concentrations of asymmetrical NG,NG-dimethyl-L-arginine and symmetrical NG,N'G-dimethyl-L-arginine were tentatively estimated to be (4.7 +/- 0.3) x 10(-7) M (n = 5) and (2.3 +/- 0.3) x 10(-7) M (n = 5), respectively. A23187 (10(-7)-3 x 10(-4) M) produced a concentration-dependent relaxation of the ciliary muscle strips which had been contracted with 10(-5) M carbachol. Authentic asymmetrical NG,NG-dimethyl-L-arginine (3 x 10(-6)-3 x 10(-4) M), but not symmetrical NG,N'G-dimethyl-L-arginine (3 x 10(-4) M), inhibited the 10(-6) M A23187-induced relaxation in a concentration-dependent manner. The inhibition with asymmetrical NG,NG-dimethyl-L-arginine (10(-4) M) was reversed by an addition of 3 x 10(-3) M L-arginine, but not by 3 x 10(-3) M D-arginine. The A23187 (10(-6) M)-induced relaxation was enhanced by 3 x 10(-3) M L-arginine or superoxide dismutase (50 U ml-1), whereas it was inhibited by carboxy-PTIO (3 x 10(-4) M), a scavenger of nitric oxide, or methylene blue (10(-5) M), an inhibitor of guanylate cyclase. The carbachol-induced contraction was enhanced by asymmetrical, NG,NG-dimethyl-L-arginine (10(-5) M) and inhibited by 3 x 10(-3) M L-arginine. Any effect of prostanoid formation during the A23187-induced relaxation was ruled out by using indomethacin (10(-5) M). Sodium nitroprusside (10(-5) M), a donor of nitric oxide, also produced a relaxation, which was inhibited by methylene blue (10(-5) M) or carboxy-PTIO (3 x 10(-4) M) and was augmented by superoxide dismutase (50 U ml-1), but unaffected by asymmetrical NG,NG-dimethyl-L-arginine (3 x 10(-4) M) or L-arginine (3 x 10(-3) M). These results lead us to speculate that the nitric oxide synthesized endogenously from L-arginine may play a role for mediating relaxation of the bovine ciliary muscle and that the endogenous asymmetrical NG,NG-dimethyl-L-arginine may be involved in inhibiting the biosynthesis of nitric oxide when there are increased intracellular concentrations of the methylarginine under certain circumstances.

Animals↗

Analysis of bile acids in colon residual liquid or fecal material in patients with colorectal neoplasia and control subjects.

Bile acids are believed to play a role in the etiology of colorectal cancer. To examine the relationship between bile acids and colorectal neoplasia, bile acids in colon residual liquid or fecal material were analyzed in 18 patients with colorectal adenoma, 12 patients with colorectal cancer, and 18 healthy control subjects. High-performance liquid chromatography combined with immobilized 3 alpha-hydroxysteroid dehydrogenase in column form showed a significant elevation in the proportion of deoxycholic acid (P < 0.05), lithocholic acid (P < 0.05), secondary bile acids (deoxycholic acid plus lithocholic acid) (P < 0.02), and the chenodeoxycholic acid-lithocholic acid family (chenodeoxycholic acid plus lithocholic acid) (P < 0.05) in the colon residual liquid or fecal material of the patients with colorectal adenoma compared with proportions in the control subjects. A similar trend was noted in the patients with colorectal cancer compared to the control subjects. These findings suggested that an increase in the proportion of secondary bile acids, in particular, of lithocholic acid, was closely related to the pathogenesis of colorectal neoplasia.

Adenoma↗

Discordant splenic uptake of Tc-99m colloid and Tc-99m denatured RBC in candidiasis-endocrinopathy syndrome.

We report discordant splenic uptake of Tc-99m colloid and Tc-99m heat-denatured red blood cells (RBC) which occurred in a 21-year-old female with candidiasis-endocrinopathy syndrome. Tc-99m colloid liver-spleen imaging showed no splenic uptake, suggesting the presence of functional asplenia. A subsequent Tc-99m heat-denatured RBC study clearly revealed a small spleen with preserved sequestrating function. These results may demonstrate that the qualitative dissociation of splenic functions in processing colloid and denatured RBC in functional asplenia: the sequestration function remains while the reticuloendothelial system is impaired.

Adult↗

Studies on the regulation of the mitochondrial alpha-ketoacid dehydrogenase complexes and their kinases.

Five mitochondrial protein kinases, all members of a new family of protein kinases, have now been identified, cloned, expressed as recombinant proteins, and partially characterized with respect to catalytic and regulatory properties. Four members of this unique family of eukaryotic protein kinases correspond to pyruvate dehydrogenase kinase isozymes which regulate the activity of the pyruvate dehydrogenase complex, an important regulatory enzyme at the interface between glycolysis and the citric acid cycle. The fifth member of this family corresponds to the branched-chain alpha-ketoacid dehydrogenase kinase, an enzyme responsible for phosphorylation and inactivation of the branched-chain alpha-ketoacid dehydrogenase complex, the most important regulatory enzyme in the pathway for the disposal of branched-chain amino acids. At least three long-term control mechanisms have evolved to conserve branched chain amino acids for protein synthesis during periods of dietary protein insufficiency. Increased expression of the branched-chain alpha-ketoacid dehydrogenase kinase is perhaps the most important because this leads to phosphorylation and nearly complete inactivation of the liver branched-chain alpha-ketoacid dehydrogenase complex. Decreased amounts of the liver branched-chain alpha-ketoacid dehydrogenase complex secondary to a decrease in liver mitochondria also decrease the liver's capacity for branched-chain keto acid oxidation. Finally, the number of E1 subunits of the branched-chain alpha-ketoacid dehydrogenase complex is reduced to less than a full complement of 12 heterotetramers per complex in the liver of protein-starved rats. Since the E1 component is rate-limiting for activity and also the component of the complex inhibited by phosphorylation, this decrease in number further limits overall enzyme activity and makes the complex more sensitive to regulation by phosphorylation in this nutritional state. The branched-chain alpha-ketoacid dehydrogenase kinase phosphorylates serine 293 of the E1 alpha subunit of the branched-chain alpha-ketoacid dehydrogenase complex. Site-directed mutagenesis of amino acid residues surrounding serine 293 reveals that arginine 288, histidine 292 and aspartate 296 are critical to dehydrogenase activity, that histidine 292 is critical to binding the coenzyme thiamine pyrophosphate, and that serine 293 exists at or in close proximity to the active site of the dehydrogenase. Alanine scanning mutagenesis of residues in the immediate vicinity of the phosphorylation site (serine 293) indicates that only arginine 288 is required for recognition of serine 293 as a phosphorylation site by the branched-chain alpha-ketoacid dehydrogenase kinase. Phosphorylation appears to inhibit dehydrogenase activity by introducing a negative charge directly into the active site pocket of the E1 dehydrogenase component of the branched-chain alpha-ketoacid dehydrogenase complex. A model based on the X-ray crystal structure of transketolase is being used to predict residues involved in thiamine pyrophosphate binding and to help visualize how phosphorylation within the channel leading to the reactive carbon of thiamine pyrophosphate inhibits catalytic activity. The isoenzymes of pyruvate dehydrogenase kinase differ greatly in terms of their specific activities, kinetic parameters and regulatory properties. Chemically-induced diabetes in the rat induces significant changes in the pyruvate dehydrogenase kinase isoenzyme 2 in liver. Preliminary findings suggest hormonal control of the activity state of the pyruvate dehydrogenase complex may involves tissue specific induced changes in expression of the pyruvate dehydrogenase kinase isoenzymes.

3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)↗

Effect of nicotine on the intimal hyperplasia after endothelial removal of the rabbit carotid artery.

1. The present experiments were designed to investigate the effect of long-term oral nicotine (10 mg/200 ml/kg/day for 7 weeks) on the intimal hyperplasia after endothelial removal of the rabbit carotid artery. 2. The plasma concentrations of nicotine were determined to be 11.7-12.5 ng/ml during the term of administration and corresponded to the plasma levels in human smokers. 3. Six weeks after the endothelial removal, light microscopy revealed a marked intimal hyperplasia. Administration of nicotine tended to accelerate the intimal hyperplasia, which was estimated by comparing the histological findings, DNA content and wet weight of the vessel wall. 4. Acetylcholine- and A23187-induced endothelium-dependent relaxations were greatly impaired in the hyperplastic artery strips. The impairment of relaxations tended to be accelerated in the nicotine group. Sodium nitroprusside-induced relaxation was not different between the control and the hyperplastic artery strips and remained unaffected in the nicotine group. 5. The concentrations of endogenous nitric oxide (NO) synthesis inhibitors, NG-monomethyl-L-arginine (L-NMMA) and asymmetrical NG,NG-dimethyl-L-arginine (ADMA) were significantly more increased in the regenerated endothelial cells compared with those in the control endothelial cells. The concentrations of L-NMMA and ADMA in the regenerated endothelial cells were significantly increased by as much as 1.3 x 10(-6) and 5.6 x 10(-7) M, respectively, in the nicotine group. 6. Immunoreactive endothelin-1 was significantly increased in the hyperplastic vessel wall (2.4 times that of the control) in 6 weeks. Administration of nicotine tended to increase the level. 7. It seems possible to assume from these results that, although, under the present experimental conditions, nicotine exhibited a tendency to accelerate the intimal hyperplasia after endothelial removal, the longer exposure to nicotine or a higher dose of the agent or both would significantly accelerate the intimal hyperplasia through the enhanced impairment of endothelium-derived relaxing factor/ NO production, which might be brought about by the enhanced increases in L-NMMA and ADMA concentrations, and the enhanced increase in endothelin-1 in the vessel wall.

Animals↗

The mechanism of myometrial contractions induced by endothelin-1 in rat.

Experiments were performed to characterize endothelin-1-induced contractions and the role of endothelin (ET) receptor subtypes in rat myometrium. The binding sites of [(125)I]-ET-1 were saturable with high affinity. Scatchard plot analysis revealed that ET-1 binding sites in the myometrium constituted a single population. The dissociation equilibrium constant (Kd) and the maximum binding sites (Bmax) were determined to be 48.9+/-3.0 pM and 1364.0+/-210.3 fmol/mg protein respectively. Specific [(125)I]-ET-1 binding was inhibited completely by unlabelled ET-1 and Ro 46-2005 (mixed-type ET receptor antagonist), but not fully (90.7+/-1.4%) by BQ 123 (a selective ETA receptor antagonist), and not at all by RES 701-1 (a selective ETB receptor antagonist). ET-1 induced myometrial contractions were composed of two types, an increase in resting tone and rhythmic contractions. These contractions were inhibited by BQ 123 and Ro 46-2005, but not by RES 701-1. ET-1-induced contractions were greatly reduced in Ca2+-free Krebs' solution. Nifedipine abolished the rhythmic contractions without affecting the increase in resting tone. These results suggest that ETA receptors are predominantly localized in rat myometrium and that excitation of ETA receptors evokes two types of contractions by increasing the cytoplasmic Ca2+ concentration.

Animals↗

Anatomy of pharynx in patients with obstructive sleep apnea and in normal subjects.

Anatomic abnormalities of the pharynx are thought to play a role in the pathogenesis of obstructive sleep apnea (OSA), but their contribution has never been conclusively proven. The present study tested this anatomic hypothesis by comparing the mechanics of the paralyzed pharynx in OSA patients and in normal subjects. According to evaluation of sleep-disordered breathing (SDB) by nocturnal oximetry, subjects were divided into three groups: normal group (n = 17), SDB-1 (n = 18), and SDB-2 (n = 22). The static pressure-area relationship of the passive pharynx was quantified under general anesthesia with complete paralysis. Age and body mass index were matched among the three groups. The site of the primary closure was the velopharynx in 49 subjects and the oropharynx in only 8 subjects. Distribution of the location of the primary closure did not differ among the groups. Closing pressure (PC) of the velopharynx for SDB-1 and SDB-2 groups (0.90 +/- 1.34 and 2.78 +/- 2.78 cmH2O, respectively) was significantly higher than that for the normal group (-3.77 +/- 3.44 cmH2O; P < 0.01). Maximal velopharyngeal area for the normal group (2.10 +/- 0.85 cm2) was significantly greater than for SDB-1 and SDB-2 groups (1.15 +/- 0.46 and 1.06 +/- 0.75 cm2, respectively). The shape of the pressure-area curve for the velopharynx differed between normal subjects and patients with SDB, being steeper in slope near Pc in patients with SDB. Multivariate analysis of mechanical parameters and oxygen desaturation index (ODI) revealed that velopharyngeal Pc was the only variable highly correlated with ODI. Velopharyngeal Pc was associated with oropharyngeal Pc, suggesting mechanical interdependence of these segments. We conclude that the passive pharynx is more narrow and collapsible in sleep-apneic patients than in matched controls and that velopharyngeal Pc is the principal correlate of the frequency of nocturnal desaturations.

Adult↗

Urinary excretion of mefenamic acid and its metabolites including their esterglucuronides in preterm infants undergoing mefenamic acid therapy.

Urinary excretion of mefenamic acid (MA) and its two oxidative metabolites, M-I (3'-hydroxymethyl derivative) and M-II (3'-carboxyl derivative), and their glucuronides was investigated in preterm infants undergoing MA therapy. MA was given orally at a dose of 2 mg/kg and the dose was repeated every 24 h a maximum of three times. Urine was collected for up to 5 d after the last dose, and MA and the metabolites were determined by a newly developed HPLC. The cumulative amounts of MA and the metabolites excreted in the urine varied from 7 to 46% of the total dose administered, and were less than those reported in adults and children. Significant correlation was observed between the plasma half-life of MA and the cumulative amount of MA and the metabolites excreted in the urine. These results suggest that long plasma half-lives of MA observed in preterm infants are due mainly to low activity of drug metabolizing enzyme(s). In an infant who received the two regimens of MA therapy about 2 weeks apart, the plasma half-life of MA was shortened and the urinary excretion of the MA metabolites including their glucuronides was greatly increased during this period. It is suggested that the activities of both cytochrome P-450(s) and glucuronyltransferase(s) related to MA metabolism rapidly increased during the first month of the infant's life.

Anti-Inflammatory Agents, Non-Steroidal↗

Abnormal modulation of cholinergic neurotransmission by endogenous nitric oxide in the bronchus of rats with hyperresponsiveness induced by allergen challenge.

The involvement of endogenous nitric oxide (NO) in bronchial cholinergic neurotransmission was compared between normal rats and airway hyperresponsive (AHR) rats. Male Wistar rats were sensitized and repeatedly challenged with dinitrophenylated (DNP)-Ascaris antigen. Twenty-four hours after the last antigenic challenge, enhancements of both the electrical field stimulation (EFS)-induced bronchoconstriction and acetylcholine (ACh) release were observed. NG-Monomethyl-L-arginine (L-NMMA; NO synthase inhibitor, 0.1 mM) augmented the EFS-induced bronchoconstriction and ACh release without affecting exogenously applied ACh-induced bronchoconstriction in normal rats. Interestingly, the augmentative effects of L-NMMA seen in normal rats were not manifested in AHR rats. Sodium nitroprusside inhibited the EFS-induced bronchoconstriction in a concentration-dependent manner; the inhibition was much larger than that of exogenously applied ACh-induced constriction in both normal and AHR rats. Furthermore, dibutyryl cGMP (3 mM) inhibited the EFS-induced bronchoconstriction with no effect on the ACh-induced bronchoconstriction in both normal and AHR rats. These findings suggest that endogenous NO may have a modulatory role in bronchial cholinergic neurotransmission in normal rats and that the augmented ACh release in the AHR rats may result from the defect of endogenous NO-induced modulation of cholinergic nerve transmission.

Acetylcholine↗

Significance of serum iron and ferritin in patients with colorectal adenomas.

BACKGROUND: Colorectal adenomas are often detected on mass screening, although detection rates with fecal occult blood tests are low. The relationship between colorectal adenomas and the resulting blood loss was examined indirectly, using serum iron and ferritin levels. METHODS: Serum iron and ferritin concentrations were measured in 184 men with colorectal adenomas (> or = 1 cm in 92; < 1 cm in 92) and in 92 healthy male controls. Values in the three groups were compared. In the patients with adenomas > or = 1 cm, serum iron and ferritin levels were compared on the basis of the site, number, histology, and degree of dysplasia of the adenoma. RESULTS: The mean serum iron level was significantly lower in patients with adenomas > or = 1 cm than in controls (P < 0.05), although this level did not differ significantly between those with adenomas < 1 cm and controls. The mean serum ferritin level also was significantly lower in patients with adenomas > or = 1 cm than in those with adenomas < 1 cm and controls (P < 0.05, P < 0.01, respectively), although this level did not differ between those with adenomas < 1 cm and controls. There was no difference in mean serum iron or ferritin levels on the basis of the site, number, histology, or degree of dysplasia of the adenoma. CONCLUSIONS: We conclude that decreased serum iron and ferritin levels are related only to adenoma size and that adenomas > or = 1 cm may bleed steadily, resulting in iron deficiency. However, low dietary intake of iron and fiber may be one of the causes of low serum iron and ferritin.

Adenoma↗

[Guided tissue regeneration around dental implants in immediate extraction sockets: comparison of resorbable and nonresorbable membranes].

OBJECTIVE: This study was performed to compare the efficacy of guided tissue regeneration (GTR) around dental implants immediately placed into extraction sockets by resorbable or nonresorbable membranes. METHODS: Mandibular P2, P3, and P4 of four adult beagle dogs were extracted bilaterally, and buccal standard defects were created and measured. Eighteen commercially pure titanium Steri-Oss implant fixtures were placed into the fresh extraction sockets. Four untreated implants were as controls, four implants received polytetrafluoroethylene (e-PTFE, Gore-Tex) membranes, five implants received collagen membranes, and five implants received polyglactin 910 mesh. After 14 weeks, clinical measurements were taken and the dogs were sacrificed and all specimens retrieved for histologic and histomophometric evaluation. RESULTS: The average gain in bone height was 2.1 mm for untreated control sites, 3.3 mm for Gore-Tex sites, 3.8 mm for collagen sites, and 1.3 mm for polyglactin 910 sites. CONCLUSION: The results of this study indicated that Gore-Tex and collagen membrane produced good results for GTR around implants. Collagen membrane can be a valid alternative to Gore-Tex membrane to improve bone regeneration around dental implants, while polyglactin 910 mesh seemed not suitable to be used as GTR membrane in immediate implantation for its high infection rate.

Animals↗

Guided tissue regeneration around dental implants in immediate extraction sockets: comparison of resorbable and nonresorbable membranes.

This study was performed to compare the efficacy of guided tissue regeneration (GTR) around dental implants immediately placed into extraction sockets by resorbable of nonresorbable membranes. Mandibular P2, P3, and P4 of four adult beagle dogs were extracted bilaterally, and buccal standard defects were created and measured. Eighteen commercially pure titanium Steri-Oss implant fixtures were placed into the fresh extraction sockets. Four implants were untreated controls, four implants received polytetrafluoroethylene (e-PTFE, Gore-Tex) membranes, five implants received collagen membranes (ParaGuide), and five implants received polyglactin 910 mesh (Vicryl). After 14 weeks, clinical measurements were taken and the dogs were sacrificed and all specimens retrieved for histologic and histomorphometric evaluation. The average gain in bone height was 2.1 mm for untreated control sites, 3.3 mm for Gore-Tex sites, 3.8 mm for collagen sites, and 1.3 mm for polyglactin 910 sites. The greatest gain in bone height and volume was seen for two sites that received Gore-Tex membranes and remained covered for the entire evaluation interval. The results of this study indicate that Gore-Tex and collagen membrane produced good results for GTR around implants immediately placed into extraction sockets. Since collagen membrane does not cause obvious infection and does not need the surgical reentry for membrane removal, it can be a valid alternative to Gore-Tex membrane to improve bone regeneration around dental implants, while polyglactin 910 mesh seems not suitable to be used as GTR membrane in immediate implantation for its high infection rate.

Animals↗

Urine N-acetyl-beta-D-glucosaminidase activity in healthy cattle.

OBJECTIVE: To measure urine N-acetyl-beta-D-glucosaminidase (NAG) activity of healthy cattle, using 3 substrates (4-methylumbelliferyl-N-acetyl-beta-D-glucosaminide, sodio-m-cresolsulfonphthaleinyl-N-acetyl-beta-D-glucosaminid e, and p-nitrophenyl-N-acetyl-beta-D-glucosaminide), and to determine the relations between the obtained values and age and sex of cattle. ANIMALS: 50 healthy lactating Holstein-Friesian cows and 10 healthy Holstein-Friesian steers. PROCEDURE: Untimed urine samples were collected, and urine NAG activity was measured, using the 3 aforementioned methods. Urine creatinine concentration also was measured, and NAG activity was expressed as units per gram of creatinine (NAG index). Correlations between urine NAG activity and age and sex of cattle were investigated. Furthermore, correlations among data obtained by each of the 3 methods were determined. RESULTS: Urine NAG activity in cows measured by each of the 3 methods was < 3.0 U/L. Urine NAG activity in steers was significantly higher than that in cows. However, there was no significant difference between the sexes in NAG index. There were no significant differences in mean values of NAG activity and index among cows of various age groups. Individual values of urine NAG activity determined by each method correlated significantly with each other. CONCLUSIONS AND CLINICAL RELEVANCE: Urine NAG activity and NAG index of healthy cattle will be useful for determining diagnostic criteria of renal disease in cattle.

Acetylglucosaminidase↗

[Cleidocranial dysplasia: a case report].

A 3-month-old female infant who presented with patent sagittal suture and loss of weight is described. Physical examination revealed a large sagittal and metopic suture showing delayed closure, a high-arched palate, saddle nose, hypertelorism and nonpalpable edges of the bilateral clavicles. The clavicles also showed undue mobility. Radiological investigations of the cranial skeletal abnormalities revealed enlargement of the sagittal and metopic sutures, and the anterior and posterior fontanelles. A chest radiograph showed a small, bell-shaped thoracic rib cage with partial aplasia of both clavicles. On the basis of the clinical findings, cleidocranial dysplasia was diagnosed. Cleidocranial dysplasia is an uncommon generalized skeletal disorder which, as its name implies, shows striking involvement of the cranial vault and clavicles. The clinical features reflect a generalized defect of both membranous and endochondral bone formation. It is characterized by delayed ossification of the skull, aplastic or hypoplastic clavicles, delayed deciduous dentition, and hereditary characteristics. The amount of calvarial growth is generally small, and the shape remains nearly unaltered. In all cases, calvarial bone thickness increases with age, but in the midline, the fontanelle area, which is shown to be defective at the first examination, remains open in all cases. The midfrontal area is poorly developed and exhibits a groove in many patients. It is inherited as an autosomal dominant trait, with wide variability of expression but a high degree of penetrance. Cytogenetic abnormalities involving chromosome 6p21 have been reported with a cleidocranial dysplasia phenotype. Although psychosocial disorders associated with the abnormal facial and body features may occur, patients have a good overall prognosis and life expectancy. Skull deformity, and delayed closure of the fontanelles and cranial sutures are the most important problems for neurosurgeons. The postero-lateral fontanelle closes before adulthood, whereas the opening in the midfrontal sutural area may persist. Many children with cleidocranial dysplasia whom we have encountered have persisting fontanelles and patent sutures, but this does not seem to predispose them to an abnormal calvarial growth pattern, at least in the age groups investigated. Congenital midface retrusion in the presence of relative or absolute mandibular prognathism is also a major deformity. Care is supportive, including attention to neurosurgical, orthopedic, pediatric and dental problems.

Cleidocranial Dysplasia↗

[Prostate cancer associated with long-term intake of patent medicine containing methyltestosterone: a case report].

An 81-year-old man, admitted with lumbago and pollakisuria, was diagnosed to have stage D2 prostate cancer (T3N2M1). Although the serum level of prostate specific antigen (PSA) was 3,560 ng/ml, serum testosterone (55.6 ng/dl) and luteinizing hormone (LH, 0.8 mIU/ml) levels were very low. Detailed inquiry of the patient revealed a daily intake of patent medicine containing 6-9 mg methyltestosterone for the past 30 years. He was treated by surgical castration and oral chlormadinone acetate. We advised him not to take such androgenic drugs. The disease has been well controlled for 7 months. We stress the importance of checking medication habits of patients with prostate cancer, especially androgen-containing drugs which can be purchased without a physician's prescription. A low serum LH level may be an important finding indicating the intake of androgenic drugs.

Aged↗

Specific accumulation of tumor-derived adhesion factor in tumor blood vessels and in capillary tube-like structures of cultured vascular endothelial cells.

Tumor-derived adhesion factor (TAF) was previously identified as a cell adhesion molecule secreted by human bladder carcinoma cell line EJ-1. To elucidate the physiological function of TAF, we examined its distribution in human normal and tumor tissues. Immunochemical staining with an anti-TAF monoclonal antibody showed that TAF was specifically accumulated in small blood vessels and capillaries within and adjacent to tumor nests, but not in those in normal tissues. Tumor blood vessel-specific staining of TAF was observed in various human cancers, such as esophagus, brain, lung, and stomach cancers. Double immunofluorescent staining showed apparent colocalization of TAF and type IV collagen in the vascular basement membrane. In vitro experiments demonstrated that TAF preferentially bound to type IV collagen among various extracellular matrix components tested. In cell culture experiments, TAF promoted adhesion of human umbilical vein endothelial cells to type IV collagen substrate and induced their morphological change. Furthermore, when the endothelial cells were induced to form capillary tube-like structures by type I collagen, TAF and type IV collagen were exclusively detected on the tubular structures. The capillary tube formation in vitro was prevented by heparin, which inhibited the binding of TAF to the endothelial cells. These results strongly suggest that TAF contributes to the organization of new capillary vessels in tumor tissues by modulating the interaction of endothelial cells with type IV collagen.

Cell Adhesion↗